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Chlorpromazine-induced cataract and corneal pigmentation
Chlorpromazine (CPZ) is a low-potency neuroleptic used
in the treatment of various psychiatric disorders.1 Chlorpro-
mazine-induced cataract and corneal pigmentation was first
described by Greiner & Berry in 1964.2 The prevalence in pa-
tients treated over time with large doses of CPZ therapy, ranges
from 15% to 74%. Though other low-potency neuroleptics like
thioridazine and fluphenazine have been reported to cause
pigmentary changes, characteristic corneal and lenticular pig-
mentation is predominantly if not exclusively a side-effect of
CPZ. We report a case of a 45-year-old female with ocular
effects due to long-term CPZ therapy for bipolar disease.
Case report
A 45-year-old female had been taking treatment for manic-
depressive psychosis with chlorpromazine 300 mg per day for
25 years. In addition, she was found to have received lithium
300 mg and haloperidol 5 mg, both twice daily for florid psy-
chotic symptoms. She came with a complaint of hazy vision of
9 months duration. On examination she had a visual acuity of
6/36 in both eyes. Penlight examination revealed a clear cor-
nea with opacity in the center of the lens in both eyes. Slit-
lamp examination revealed pigment dusting over the back of
the cornea, which was diffuse, granular, and brown in color,
most prominent at the level of deep stroma and endothelium.
There was a star-shaped anterior polar cataract, which was
golden brown in color involving the anterior capsule and sub-
capsular epithelium, characterizing Grade IV lenticular pig-
mentation (Figure 1). The rest of the lens was clear. The distri-
Figure 1: Stellate cataract caused by chlorpromazine therapy.
Case
Report
bution was symmetrical in both eyes. Two independent clini-
cians documented the condition. The pupils were dilated with
1% tropicamide for retinoscopy. A dilatation of only 4 mm could
be achieved. Fundus examination by indirect ophthalmoscopy
was normal. Systemic examination was normal; apart from a
few extrapyramidal symptoms there were no other side-ef-
fects of CPZ, including skin discoloration. Investigations in-
cluding liver function tests and peripheral smear were nor-
mal. With subjective correction, the patients vision improved
to 6/9. With the psychiatrists consultation, CPZ was substi-
tuted with trifluoperazine.
Discussion
Chlorpromazine is an aliphatic phenothiazine used in all
types of psychosis, especially schizophrenia. The adverse ef-
fects include drowsiness, lethargy, postural hypotension, an-
ticholinergic side-effects, infertility and extrapyramidal symp-
toms, which are dose-related. The hypersensitivity reactions
are cholestatic jaundice, skin rashes, photosensitivity and
agranulocytosis. Blue pigmentation of exposed skin, corneal
and lenticular opacities and retinal degeneration occur rarely
after long-term use of high doses of phenothiazines. The most
prevalent ocular side-effect associated with CPZ therapy is
anterior capsular and subcapsular lens pigmentation, followed
by corneal endothelial pigmentary changes. Alexander and
associates found 67% of a group of patients to have the former,
while 45% exhibited the latter.1 However, both conditions rarely
reduce visual acuity, and patients may occasionally report glare
and halos around lights. Thaler and associates described len-
ticular pigmentation as occurring in 5 stages.3 They range from
isolated, brownish, dust-like specks in the anterior surface of
the lens to stellate cataracts that can impair visual acuity. The
stellate pattern, which characterizes Grade IV lenticular
changes, has a dense central area with radiating branches as
seen in our patient. The lens changes at this stage can be rec-
ognized with a penlight, and diagnosis does not necessarily
require slit-lamp examination.
Corneal pigmentary changes almost invariably occur in
patients who have concomitant lens opacities in the higher
grades.3 The pigmentation is white, yellow-white, brown, or
black and occurs at the level of the endothelium and Descemets
membrane, primarily in the interpalpebral area and may also
occur in the epithelial layer. There is often little or no corneal
involvement with lens opacities Grades I and II, but Grades III
and higher have detectable corneal pigmentation ranging from
light to heavy. In severe cases it can affect the deep stroma.
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Case Report
The reported frequency of lenticular opacities is influenced
by the nature of the population and by the examining ophthal-
mologists familiarity with the entity. These changes occur with
low-potency neuroleptics such as CPZ or thioridazine and are
dose-related. Lenticular pigmentation is rarely evident when
the total cumulative dosage is less than 500 g, and the preva-
lence of pigmentary changes increases with total dosage be-
tween 1000 and 2000 g.1,3 Since some psychiatric conditions
may require daily dosages exceeding 800 mg, lenticular pig-
mentation can appear in as early as 14 to 20 months of
therapy.3 Dosages consisting of 2000 mg daily have caused
lenticular changes in as early as 6 months of therapy.
Lithium is known to increase extrapyramidal symptoms,
increase risk of derilium and malignant neuroleptic syndrome
when combined with CPZ though there is no documented evi-
dence of increasing its ocular side-effects. The other ocular
changes that can occur with CPZ toxicity are discoloration of
the conjunctiva, sclera, skin of the lids and pigmentary changes
in fundus, which were not there in this patient. Poor mydriasis
noted in this patient is probably due to the infiltration of the
dilator pupillae muscle of the iris by pigments.
Chlorpromazine deposition in high levels can cause de-
creased visual acuity and significant skin discoloration.4 Sur-
prisingly, in our patient, though the cumulative total dose ex-
ceeded 2500 g, there was no skin discoloration. It is suggested
that only individuals with impaired glucuronide conjugation of
CPZ and its metabolites are susceptible to skin changes. An-
other postulation could be the protective effect of haloperidol
though the exact mechanism is unknown. Furthermore, pho-
tosensitivity of the skin to the sun without increase in skin
pigmentation is much more common and has a significant re-
lationship with eye changes rather than skin pigmentation.
The precise nature of the pigmentary granules in the cor-
nea and lens is unknown. The pigmentary changes may be a
result of drug interaction with ultraviolet light as it passes
through the cornea and lens, causing exposed proteins to de-
nature, opacify, and accumulate in the anterior subcapsular
region of the lens as well as in corneal stroma.5 There is a
general agreement that the pigment deposited is melanin, prob-
ably combined with the neuroleptic or one of its metabolites.
Usually, the corneal and lenticular pigmentary changes
progress to a point beyond which no further changes are ob-
served. On reduction or discontinuation of drug therapy, the
pigmentary deposits are generally irreversible though some
reports of reversible epithelial keratopathy have been noted.
This may be because the deposits associated with CPZ therapy
are located in avascular tissues. In rare instances the lenticu-
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324 Indian J Pharmacol | October 2004 | Vol 36 | Issue 5 | 323-324
lar pigmentation can begin after CPZ therapy is discontinued.
The differential diagnosis includes axial punctate opaci-
ties that are found in about 10% of all normal individuals over
the age of 40. We believe that individual factors like drug me-
tabolism may play a role in susceptibility to corneal and len-
ticular opacities.
Patients receiving high-dosage or long-term, low-dosage
CPZ therapy should be monitored annually by careful slit-lamp
examination. Since lens pigmentation is the most frequent
ocular change observed, slit-lamp examination of the lens with
the pupil dilated is the most direct method for detecting early
CPZ toxicity. It is believed that the ocular changes do not oc-
cur with higher potency neuroleptics such as haloperidol and
trifluoperazine. Though the ocular changes do not reverse even
when CPZ is withdrawn, the institution of high-potency
neuroleptics would at least arrest the progress of the opaci-
ties. The use of spectacle lenses, presumably to reduce the
amount of ultraviolet light entering the eye, has been unsuc-
cessful in reducing the prevalence of ocular toxicity.1 The use
of d-penicillamine has also not been found to be successful in
reversing the ocular pigmentary changes associated with long-
term CPZ therapy.
If corneal and lens changes occur but visual acuity is not
affected and the patient is asymptomatic, the drug dosage can
be continued without modification. If the patient becomes
symptomatic, the dosage should be reduced or therapy should
be changed to a different drug.
K. Subashini, V. A. Rao
Department of Ophthalmology, Jawaharlal Institute of
Postgraduate Medical Education and Research,
Pondicherry - 605 006, India.
E-mail: subadoc@hotmail.com
References
1. Alexander LJ, Bowerman L, Thompson LR. The prevalence of the ocular side
effects of chlorpromazine in the Tuscaloosa Veterans Administration patient
population. J Am Optom Assoc 1985;56:872-6.
2. Greiner AC, Berry K. Skin pigmentation and corneal and lens opacities with
prolonged chlorpromazine therapy. Can Med Assoc J 1964;90:663-5.
3. Thaler JS, Curinga R, Kiracofe G. Relation of graded ocular anterior chamber
pigmentation to phenothiazine intake in schizophrenics- quantification proce-
dures. Am J Optom Physiol Opt 1985;62:600-4.
4. Webber SK, Domniz Y, Sutton GL, Rogers CM, Lawless MA. Corneal deposi-
tion after high dose chlorpromazine hydrochloride therapy. Cornea 2001;20:
217-9.
5. Deluise VP, Flynn JT. Asymmetric anterior segment changes induced by chlo-
rpromazine. Ann Ophthalmol 1981;13:953-5.